More than ten millions of patients suffer from tissue defects or organ failure every year in the world, and about 8 million of the patients are treated by surgical operations each year in America only. However, living donor tissue organs are limited, and an existing mechanical apparatus does not have all functions of complicated tissue organs and cannot prevent further deterioration of diseases of the patients. In recent ten years, scientists perform in-vitro reproduction by utilizing a small amount of normal cells of residual human organs by using a tissue engineering technology, and obtain organs with the same function needed by the patients. The organs do not have a rejection reaction, and favorable results are achieved. Many newly established biotechnology companies are getting ready to invest large sums of money for realizing commercialization. An industry with a value of 4 billion dollars is formed and progressively increased at a speed of 25% per year in America. However, an existing tissue engineering technology faces many difficulties and limitations, and successes achieved by tissue engineering application research exist in tissues with relatively simple structures and physiological functions, such as skeleton and cartilage. A traditional scaffold preparation technology cannot accurately sizes, structures, space distribution and penetrating channels of pores, and nutrition supply and vascular growth are greatly limited. A structural scaffold is first prepared in a traditional tissue engineering method generally; and since most of oxygen and nutrition are consumed by upper cells in a cell culture process, these components are prevented from diffusing to a bottom layer, thereby limiting migration of the cells to a deep layer of the scaffold. Such a method for sequentially preparing the scaffold and then culturing the cells consumes time and labor, and the cells may be varied and aged in a process of migrating into the scaffold, so that a requirement of treating clinical patients in time cannot be met. Meanwhile, the traditional tissue engineering technology cannot meet needs for accurately and spatially positioning and placing different cells at fixed points and constructing functional gradient structures of the complicated tissue organs.
3D printing (three-dimensional printing, 3DP) is also called rapid prototyping (RP) or additive manufacturing (AM), thereby realizing formation of a structural body by utilizing layer-by-layer stacking of materials. Many foreign scientific research teams realize assembling or printing of a cell-containing three-dimensional structural body based on an RP technology, such as a three-dimensional fibrous deposition technology in a medical center of Utrecht University [Fedorovich N E, et al. Tissue Engineering Part C, 2011, 18(1):33], a three-dimensional direct writing bio-printing technology of University of Arizona [Cooper G M, et al. Tissue Engineering Part A, 2010, 16(5):1749], etc. A Center of Organ Manufacturing in Tsinghua University in China develops a melted extrusion modeling device and a single (double)-end nozzle (needle) low-temperature deposition forming device and successfully prepares simple vascular nets, hepatic tissues, bone repair materials and the like [Wang X H, et al. Trends in Biotechnology, 2007, 25:505; Wang X H, et al. Tissue Engineering Part B, 2010, 16:189; Wang X H. Artificial organs, 2012, 36:591].
The 3DP has many manners. For example, a porous hollow structure is prepared by utilizing the RP technology in University of Science and Technology of China and Dalian University of Technology. The porous hollow structure saves raw materials and can guarantee original characters and mechanical properties [Wang W, et al. ACM Transactions on Graphics (TOG), 2013, 32(6):177]. Vozzi G, et al. in University of Pisa prepare a hexagonal mesh by utilizing a microinjection method, and a forming structure is accurate [Vozzi G, et al. Tissue Engineering, 2002, 8(6):1089-1098]. A preparation method for preparing the above hollow structure is limited to a field of synthetic polymeric materials. An application of the preparation method in a biological and hydrogel system is seldom mentioned. An application of a hollow hydrogel structure contributes to increasing an exchange speed of a nutrient solution in the structural body.
A microfluidics technology (MT) can control, operate and detect complicated fluid under a microscopic size and emerges rapidly in fields of micromechanics, bioengineering and the like in recent years, and then a lab on a chip appears at the right moment. Capel A J, et al. in Loughborough University summarize applications of five rapid prototyping technologies in a fluid chemical reaction and propose a preparation method for preparing a small-sized reactor [Capel A J, et al. Lab on a Chip, 2013, 13(23):4583]. A combination of the 3D printing technology and the microfluidics technology is a research hotspot for solving artificial organ manufacturing. For example, Miller J S, et al. in University of Pennsylvania prepare a three-dimensional soluble sugar fiber scaffold, and the sugar fiber scaffold is introduced into blood to simulate an effect of a shear force, thereby completing adhesion of endothelial cells in a vessel channel and realizing a primary vascular function [Miller J S, et al. Nature materials, 2012, 11(9):768]. However, preparation of the sugar fiber scaffold consumes time and labor, and precision and geometry complexity are also limited.
A patent literature (with an application number of 201210324600.4) proposes a method for preparing a spindle-shaped complex organ precursor by using a rotary composite mold. According to the method, an arc at a periphery of a formed body is obtained through relative rotation of the mold, and a semi-spindle-shaped formed body with branch channels is obtained through a pouring method. However, in the method, controllability of fine structures of the branch channels is low, multiple branches of the branch channels are difficult to be guaranteed, and operating stability, structural complexity and the like remain to be improved.
A patent literature (with an application number of 201410026170.7) proposes a rapid prototyping method for preparing a vascularized tissue structure with a microfluidic channel. The structure prepared by the method only contains a one-in one-out branch vessel system, cannot satisfy a need that a complex organ simultaneously contains branch artery and vein vascular systems and a nervous system, and cannot ensure that the constructed vascularized tissue structure has strong growth ability and metabolic functions after transplanted in vivo.
Through the above analysis, construction of a full-function artificial organ by utilizing a regenerative medicine principle has become a research hotspot in medicine and engineering fields. The existing 3DP (AM), microfluidics technology and a combined mold technology cannot prepare a full-function implantable organ structure capable of simultaneously containing the branch artery and vein vascular system, the nervous system and an immune system and capable of being directly connected with human artery and vein vessels, nerves and other systems. These factors promote an organic combination of various different technologies, and full-function artificial organs with various system structures are prepared by utilizing a composite multi-nozzle 3D printing technology, in-mold pouring, spraying, electrospining and other technologies, thereby realizing composite forming of various biological materials including high polymer solutions, cell-containing hydrogel and cell-containing dilute solutions. The various systems distributed in the organs may be mutually promoted and synergetically developed. The present invention establishes a theoretical and practical foundation for manufacturing the full-function artificial organs.